Project Summary Failure of the ductus arteriosus (DA), a vessel connecting the pulmonary artery to the aorta, to close after birth results in significant morbidity in premature infants. As many as 60% of newborns delivered prior to 28 weeks gestation will require therapy to close their patent DA. Administration of non-steroidal antiinflammatory agents, such as indomethacin is the preferred initial therapy. However, development of acute kidney injury (AKI) commonly occurs as a result this pharmacologic therapy. Development of renal impairment, including decreased urine output, results in: 1) water retention that may impair ductal closure, 2) limitation of nutritional fluid intake, 3) interruption of the three-dose course of treatment with resultant treatment failure; and 4) potential risk for long term renal injury. Alleviating the severity of renal impairment associated with indomethacin would significantly reduce neonatal morbidity. Fenoldopam is a selective dopamine type 1 receptor agonist with the potential to dilate the renal vasculature and maintain renal blood flow and function. In critically ill adults and postoperative pediatric cardiac surgical patients, fenoldopam preserves renal function compared to placebo. Studies in neonates are limited. Demonstration of beneficial effects in the preterm infant would have a vast impact on clinical care in this population. Our primary hypothesis is that fenoldopam reduces renal dysfunction associated with indomethacin administration for closure of patent DA in preterm infants. A secondary outcome will be the determination of fenoldopam pharmacokinetics in the premature population. Our study will also allow us to determine whether newly identified biomarkers of AKI, such as urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, or novel metabolites, are more sensitive markers of renal dysfunction than traditional markers including urine output and serum creatinine. The prospective design of the study and ability to obtain samples prior to administering a renal toxic agent affords us this opportunity. We will conduct a prospective, blinded, randomized, placebo-controlled trial with a sample size of 20 patients in each of the two arms (fenoldopam vs placebo) based upon a difference in serum creatinine by one standard deviation. The primary outcome will be a reduction in AKI, as determined by creatinine and urine output. Identification of a medication that preserves renal function in the preterm infant will have an immediate impact on reducing short term morbidities associated with prematurity. Studies also suggest avoidance of acute kidney injury in neonates will likely lessen the burden of chronic disease later in life.